Sex differences in posttraumatic cytokine release of endotoxin-stimulated whole blood: relationship to the development of severe sepsis.

Abstract

In experimental trauma-hemorrhage and sepsis, a sexual dimorphism of cell-mediated immune functions has been described, which has been related to higher susceptibility to and mortality from sepsis in males. Therefore, in the present study, sex differences with regard to cytokine release of endotoxin stimulated whole blood and its relation to the development of severe posttraumatic sepsis were investigated in blunt trauma patients with multiple injuries. Eighty-four patients (25 female; 59 male) sustaining blunt injuries with an Injury Severity Score > 16 were enrolled in the study. Whole blood and serum were obtained during a 14-day period of hospitalization. The capacity of peripheral blood mononuclear cells to produce cytokines (tumor necrosis factor-alpha, interleukin [IL]-6, IL-8) was tested by using a whole blood assay. Serum samples were assayed for anti-inflammatory cytokines (IL-4, IL-10, and transforming growth factor beta1) and sex hormones (testosterone, estradiol, progesterone). Patients were monitored daily for sepsis criteria according to the ACCP/ SCCM consensus conference 1992. Within the entire patient population, sex differences in posttraumatic cytokine release were not detectable. Male trauma patients developing severe sepsis (n = 16) presented with a significantly increased cytokine producing capacity in the early posttraumatic period (< or = 24 hours after admission to the emergency room) when compared with males with an uncomplicated recovery. In females, differences between the subgroups of patients with (n = 7) and without development of severe sepsis were not detectable. There were no differences in systemic levels of anti-inflammatory cytokines within the early posttraumatic period between the subgroups of male and female patients with and without development of severe sepsis. In females, differences in sex hormone levels were not detectable, whereas in males, development of severe sepsis later was found to coincide with significantly decreased testosterone and increased estradiol serum levels. The present study demonstrates a sex-specific regulation of leukocyte function in patients with multiple injuries within the early posttraumatic period. In male patients with multiple injuries, increased cytokine-producing capacities may correspond to enhanced inflammatory responses, which increase susceptibility to sepsis, whereas in female patients, other regulatory mechanisms may be involved.